A novel murine long-chain acyl-CoA synthetase expressed in brain participates in neuronal cell proliferation

Refsum disease (RfD) is an autosomal recessive neurologic disorder of the lipid metabolism. We have identified a novel murine long-chain acyl-CoA synthetase (mLACS) associated with the RfD gene using yeast two-hybrid assay. Northern blot analyses revealed that mLACS was expressed mainly in the brain and testis. mLACS was highly expressed in the brain at 2 weeks after birth and maintained through adult life. Expressions of the brain-specific LACS family increased in the PC12 cells undergoing neurite outgrowth by nerve growth factor. mLACS preferentially catalyzed the formation of arachidonoyl-CoA more than palmitoyl-CoA or oleoyl-CoA in PC12 cells. Triacsin C, an inhibitor of LACS, suppressed the cell proliferation and decreased mLACS expression in parent PC12 cells, but not in stably anti-sense mLACS cDNA-transfected cells. Our results indicate that mLACS participates in neuronal cell proliferation and differentiation, and interaction of the RfD gene with brain-selective mLACS may be involved in the pathogenesis of RfD.